Homeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly
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Homeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly. / Tsujita, Kazuya; Satow, Reiko; Asada, Shinobu; Nakamura, Yoshikazu; Arnes, Luis; Sako, Keisuke; Fujita, Yasuyuki; Fukami, Kiyoko; Itoh, Toshiki.
In: Nature Communications, Vol. 12, No. 1, 5930, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Homeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly
AU - Tsujita, Kazuya
AU - Satow, Reiko
AU - Asada, Shinobu
AU - Nakamura, Yoshikazu
AU - Arnes, Luis
AU - Sako, Keisuke
AU - Fujita, Yasuyuki
AU - Fukami, Kiyoko
AU - Itoh, Toshiki
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - Malignancy is associated with changes in cell mechanics that contribute to extensive cell deformation required for metastatic dissemination. We hypothesized that the cell-intrinsic physical factors that maintain epithelial cell mechanics could function as tumor suppressors. Here we show, using optical tweezers, genetic interference, mechanical perturbations, and in vivo studies, that epithelial cells maintain higher plasma membrane (PM) tension than their metastatic counterparts and that high PM tension potently inhibits cancer cell migration and invasion by counteracting membrane curvature sensing/generating BAR family proteins. This tensional homeostasis is achieved by membrane-to-cortex attachment (MCA) regulated by ERM proteins, whose disruption spontaneously transforms epithelial cells into a mesenchymal migratory phenotype powered by BAR proteins. Consistently, the forced expression of epithelial–mesenchymal transition (EMT)-inducing transcription factors results in decreased PM tension. In metastatic cells, increasing PM tension by manipulating MCA is sufficient to suppress both mesenchymal and amoeboid 3D migration, tumor invasion, and metastasis by compromising membrane-mediated mechanosignaling by BAR proteins, thereby uncovering a previously undescribed mechanical tumor suppressor mechanism.
AB - Malignancy is associated with changes in cell mechanics that contribute to extensive cell deformation required for metastatic dissemination. We hypothesized that the cell-intrinsic physical factors that maintain epithelial cell mechanics could function as tumor suppressors. Here we show, using optical tweezers, genetic interference, mechanical perturbations, and in vivo studies, that epithelial cells maintain higher plasma membrane (PM) tension than their metastatic counterparts and that high PM tension potently inhibits cancer cell migration and invasion by counteracting membrane curvature sensing/generating BAR family proteins. This tensional homeostasis is achieved by membrane-to-cortex attachment (MCA) regulated by ERM proteins, whose disruption spontaneously transforms epithelial cells into a mesenchymal migratory phenotype powered by BAR proteins. Consistently, the forced expression of epithelial–mesenchymal transition (EMT)-inducing transcription factors results in decreased PM tension. In metastatic cells, increasing PM tension by manipulating MCA is sufficient to suppress both mesenchymal and amoeboid 3D migration, tumor invasion, and metastasis by compromising membrane-mediated mechanosignaling by BAR proteins, thereby uncovering a previously undescribed mechanical tumor suppressor mechanism.
U2 - 10.1038/s41467-021-26156-4
DO - 10.1038/s41467-021-26156-4
M3 - Journal article
C2 - 34635648
AN - SCOPUS:85116762240
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5930
ER -
ID: 282742090